Cell Death and Fibrogenesis

ABSTRACT

Fibrosis is a common feature of chronic liver injury and is initiated by cell death inside the liver. Hepatocyte death results in apoptotic bodies and other cellular debris, which are phagocytosed by hepatic stellate cells (HSCs), resulting in their activation, proliferation, differentiation, and matrix deposition. This profibrotic effect of cellular death is balanced by an antifibrotic effect of HSC death. Many HSC survival signals are obtained from the extracellular matrix, and active proapoptotic signals are provided by immune cells, particularly natural killer (NK) cells. Quiescent HSCs are relatively resistant to apoptotic signals but become sensitive after activation. The important role of NK cells in inducing HSC apoptosis may explain the increased fibrosis associated with immune suppression (e.g., in the transplant recipient) and HIV infection. HSCs also undergo senescence, which limits their function and sensitizes them to apoptosis.

KEYWORDS

Hepatic stellate cells - fibrosis - cell death - apoptosis

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